Nanotechnology applications are being incorporated into our daily lives, but the safety of nanomaterials usage still awaits thorough assessment. Currently, little is known about nanomaterial-biological interactions, and to bridge this gap, I propose using embryonic zebrafish as a rapid, in vivo system to investigate the activity of nanomaterials at the molecular level. High-purity, ligand-functionalized silver nanoparticles (AgNPs) can be precisely engineered to custom-manipulate physicochemical properties. I hypothesize that the biological activity of nanomaterials is dependent upon primary particle size, size distribution, chemical composition of surface groups, surface charge and state of agglomeration. To test this hypothesis, I will collect toxicity data including morbidity and mortality dose response, uptake concentration, and nanoparticle exposure-induced changes in gene expression. Additionally, by exposing embryonic zebrafish to silver nanoparticles (AgNPs) engineered to exhibit highly specific physicochemical properties, I will define which properties are responsible for causing specific biological effects. All data will be recorded in the Nanomaterial-Biological Interactions (NBI) knowledge base. The NBI knowledgebase serves as a warehouse for annotated data on nanomaterial characterization, synthesis methods, and nanomaterial-biological interactions defined at multiple levels of biological organization. The data I submit to the NBI knowledgebase will facilitate identification of key data for predicting the biological effects of nanomaterial exposure based on physicochemical properties. PUBLIC HEALTH RELEVANCE: Structure-activity based prediction of health hazard potential of nanomaterials should be in place during technology development. Given that nanomaterials are becoming pervasive, it is imperative that science rapidly develops structure-biological activity relationships for new and emerging classes of nanomaterials. This will serve to both ensure human safety of the technology and minimize the gross inefficiency of blindly developing inappropriate uses of nanomaterials for biomedical and consumer products.